title: The presence of CXCR4-using HIV-1 prior to start of antiretroviral therapy is an independent predictor of delayed viral suppression.
abstract: The emergence of CXCR4-using HIV variants (X4-HIV) is associated with accelerated disease progression in the absence of antiretroviral therapy. However, the effect of X4-HIV variants on the treatment response remains unclear. Here we determined whether the presence of X4-HIV variants influenced the time to undetectable viral load and CD4+ T cell reconstitution after initiation of cART in 732 patients. The presence of X4-HIV variants was determined by MT-2 assay prior to cART initiation and viral load and CD4+ T cell counts were analyzed every 3 to 6 months during a three year follow-up period. Kaplan-Meier and Cox proportional hazard analyses were performed to compare time to viral suppression and the absolute CD4+ T cell counts and increases in CD4+ T cell counts during follow-up were compared for patients with and without X4-HIV at start of cART. Patients harboring X4-HIV variants at baseline showed a delay in time to achieve viral suppression below the viral load detection limit. This delay in viral suppression was independently associated with high viral load and the presence of X4-HIV variants. Furthermore, the absolute CD4+ T cell counts were significantly lower in patients harboring X4-HIV variants at all time points during follow-up. However, no differences were observed in the increase in absolute CD4+ T cell numbers after treatment initiation, indicating that the reconstitution of CD4+ T cells is independent of the presence of X4-HIV variants. The emergence of X4-HIV has been associated with an accelerated CD4+ T cell decline during the natural course of infection and therefore, patients who develop X4-HIV variants may benefit from earlier treatment initiation in order to obtain faster reconstitution of the CD4+ T cell population to normal levels.
authors.affiliation: Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Esther F
authors.initials: EF
authors.lastname: Gijsbers
authors.forename: Ard
authors.initials: A
authors.lastname: van Sighem
authors.forename: Agnes M
authors.initials: AM
authors.lastname: Harskamp
authors.forename: Matthijs R A
authors.initials: MR
authors.lastname: Welkers
authors.forename: Frank
authors.initials: F
authors.lastname: de Wolf
authors.forename: Kees
authors.initials: K
authors.lastname: Brinkman
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Angélique B
authors.initials: AB
authors.lastname: van 't Wout
authors.forename: Neeltje A
authors.initials: NA
authors.lastname: Kootstra
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015728:Receptors, HIV / Q000378:metabolism; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019718:Receptors, CXCR4; D015728:Receptors, HIV